Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors.

The most common breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) transcripts in chronic myeloid leukemia (CML) are e13a2 (b2a2) and e14a2 (b3a2). The impact of the type of transcript on response and survival after initial treatment with different tyrosine kinase inhibitors is unknown. This study involved 481 patients with chronic phase CML expressing various BCR-ABL transcripts. Two hundred patients expressed e13a2 (42%), 196 (41%) expressed e14a2, and 85 (18%) expressed both transcripts. The proportion of patients with e13a2, e14a2, and both achieving complete cytogenetic response at 3 and 6 months was 59%, 67%, and 63% and 73%, 81%, and 82%, respectively, whereas major molecular response rates were 27%, 49%, and 50% at 3 months, 42%, 67%, and 70% at 6 months, and 55%, 83%, and 76% at 12 months, respectively. Median (international scale) levels of transcripts e13a2, e14a2, and both at 3 months were 0.2004, 0.056, and 0.0612 and at 6 months were 0.091, 0.0109, and 0.0130, respectively. In multivariate analysis, e14a2 and both predicted for optimal responses at 3, 6, and 12 months. The type of transcript also predicted for improved probability of event-free (P = .043; e14a2) and transformation-free survival (P = .04 for both). Compared to e13a2 transcripts, patients with e14a2 (alone or with coexpressed e13a2) achieved earlier and deeper responses, predicted for optimal European Leukemia Net (ELN) responses (at 3, 6, and 12 months) and predicted for longer event-free and transformation-free survival.

Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities.

Early responses to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML)-chronic phase (CP) are associated with improved outcome. We analyzed the impact of such a response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. A total of 483 patients who received 400 or 800 mg imatinib, nilotinib, or dasatinib were analyzed. The median follow-up was 72 mo. Landmark analysis at 3 mo by molecular response showed that the cumulative proportions of 3-y event-free survival (EFS) for 3-mo BCR-ABL levels was 95% for those with ≤1%, 98% for >1% to 10%, and 61% for those with >10% (P = .001). The corresponding values by cytogenetic responses were 97% if Ph+ = 0%, 89% if Ph+ = 1% to 35%, and 81% if Ph+ >35% (P = .001). Cytogenetic response at 3 mo significantly discriminated for 3-y overall survival (OS): 98%, 96%, and 92%, respectively (P = .01). In multivariate analysis, young patients, high Sokal index, and treatment with imatinib 400 significantly predicted for poor (>35%) cytogenetic response at 3 mo. Early responses are predictive for EFS and failure-free survival and to a lesser extent OS, regardless of the treatment modality, although therapies other than standard-dose imatinib result in higher rates of deep early responses.

Assessing need for palliative care services for children in Mexico.

BACKGROUND: Pediatric palliative care increasingly became integrated into health care institutions worldwide over the last decade. However, in Mexico and other developing countries with large populations of children, little is known regarding the need for palliative care services. We aimed to assess the need for palliative and end-of-life care for children dying in public hospitals affiliated with Secretaria de Salud in Mexico. MEASUREMENT: We conducted a retrospective review of deaths of children (1-17 years old) occurring during 2011 and determined deaths associated with underlying complex chronic conditions by reviewing the four causes of death listed in the death certificate. We collected sociodemographic and clinical data and utilized univariate and multivariate analyses to determine factors associated with complex chronic conditions. RESULTS: A total of 2715 pediatric deaths were studied. We found 41% were associated with a complex chronic condition. The most frequent types of conditions were malignancies (47%), neuromuscular (18%), cardiovascular (12%), and renal (10%). Children with renal and malignant conditions died at an older age than children with other types of complex chronic conditions. Multivariate analysis indicated the independent predictors of death with complex chronic condition were no indigenous ethnicity, lack of admission to the intensive care unit during the final hospital stay, and having affiliation with an institution for health care. CONCLUSIONS: A large proportion of pediatric deaths are associated with complex chronic conditions indicating the provision of adequate funding for professional education and palliative care initiatives for children in Mexico, should be a topic of the national health care agenda.